This application claims priority to provisional application Ser. No. 60/757,287 filed Jan. 9, 2006, the contents of which are incorporated herein by reference.
Cell-based screening plays an important role in the detection of disease and abnormalities, as well as drug and treatment discovery. Easy and early detection still continues to be essential to treatment of disease infection.
For example, malaria infects about 400 million people each year and kills up to 3 million, most of them African children. The highest mortality is caused by the Plasmodium falciparum parasite and its merozoites (daughters) through infection of red blood cells (“RBCs”). See Ref. 5. Better tools are needed for the control and cure of malaria, but malaria remains a diagnostic challenge to laboratories in most countries. Recent efforts at intervention would benefit real time feedback on their efficacy, which has increased the need for rapid diagnostics. At the same time the higher cost of new drug treatments creates downward pressure on diagnostic costs.
To have practical impact, diagnostics that provide confirmation of suspected acute malaria in less than 1 hour would be preferred. See Ref. 6. Several techniques are currently in use, but none are ideal. See id.; see also Ref. 9. Microscopic examination of stained blood samples is currently the standard and yields fast results, but requires a high skill level and is not suitable for mass screening in endemic areas. Polymerase chain reaction (“PCR”) and fluorescent labeling methods are sensitive but take a long time for detection, use specialized equipment, and are expensive. A recent generation of “dipstick” or cassette-based immunochromatographic assays, known as Rapid Diagnostic Tests (“RDTs”) have helped move diagnosis into the field. See, e.g., Ref. 10. However, these RDTs are influenced by positive results due to causes other than malaria antigenemia, and by negative results due to causes other than low parasitemia. See id. In addition, significant issues have arisen with quality control, reliability, sensitivity to variations in temperature and humidity, shelf life, and overall cost of RDTs. These issues have led to a substantial and costly effort to establish a supporting infrastructure in certain endemic countries. See Ref. 9. Many of these issues are intrinsic to the chemistry-based assay of the RDTs. The goal of mass screening in endemic countries is far from being met.
Thus, there remains a need for cost-effective diagnostic techniques that can yield unambiguous and (semi-) quantitative results in less than an hour with detection sensitivities of less than 100 parasites/μL (i.e., the goals set forth by the World Health Organization). See Refs. 6 and 9. Even greater sensitivity and quantitative measures of parasitemia are important when monitoring treatment of chronic cases, confirming cure (parasitemia of zero), and monitoring resistance to drugs, a growing and costly problem in malaria treatment.
While challenges associated with rapid detection and the need for innovative solutions are particularly acute in the case of malaria, there is likewise a need in the art for improved methods and apparatus for the diagnosis and/or monitoring of a wide variety for diseases and abnormal conditions.